Sequential Spectrophotometric Method for the Simultaneous Determination of Amlodipine, Valsartan, and Hydrochlorothiazide in Coformulated Tablets

A new, simple and specific spectrophotometric method was developed and validated in accordance with ICH guidelines for the simultaneous estimation of Amlodipine (AML), Valsartan (VAL), and Hydrochlorothiazide (HCT) in their ternary mixture. In this method three techniques were used, namely, direct spectrophotometry, ratio subtraction, and isoabsorptive point. Amlodipine (AML) was first determined by direct spectrophotometry and then ratio subtraction was applied to remove the AML spectrum from the mixture spectrum. Hydrochlorothiazide (HCT) could then be determined directly without interference from Valsartan (VAL) which could be determined using the isoabsorptive point theory. The calibration curve is linear over the concentration ranges of 4–32, 4–44 and 6–20？μg/mL for AML, VAL, and HCT, respectively. This method was tested by analyzing synthetic mixtures of the above drugs and was successfully applied to commercial pharmaceutical preparation of the drugs, where the standard deviation is <2 in the assay of raw materials and tablets. The method was validated according to the ICH guidelines and accuracy, precision, repeatability, and robustness were found to be within the acceptable limits. 1. Introduction Many analytical methods have been introduced for the analysis of mixtures among which the molecular absorption spectroscopy was the most simple, fast, and applicable in laboratories. Molecular absorption spectroscopy has been extensively used for the determination of drugs in pharmaceutical preparations with a view to the development of analytical methods. The use of this technique for pharmaceutical analyses has the inherent constraint that most active drugs absorb in the UV region and exhibit strongly overlapped spectra that impede their simultaneous determination. Direct spectrophotometry cannot resolve the drugs in their mixtures with impurities or other drugs, so several manipulations were performed to enable resolution of binary and ternary mixtures. Binary mixtures can be determined using different order derivatives [1], methods manipulating ratio spectra [2, 3] or dual wavelength [4–6], and isoabsorptive method [7]. For ternary mixtures, few spectrophotometric methods could resolve the overlap in their spectra, namely, Derivative Ratio Zero Crossing [8] and Double Divisor Ratio Spectra-Derivative Spectrophotometry [9] methods. This paper describes the development and subsequent validation of a novel, simple, and rapid spectrophotometric method “Sequential Spectrophotometry” for simultaneous quantitation of ternary mixtures. The method was